Biomedical subjects

S P Tuck

Publications and source records attributed to S P Tuck.

5 recordsLinked to original sources

PubMed2005

Differences in bone mineral density and geometry in men and women: the Newcastle Thousand Families Study at 50 years old.

In 1947 Sir James Spence initiated the Newcastle Thousand Families study, which recruited all 1142 children born in the city between May and June that year. At the age of 50 years, 832 survivors were traced and invited to attend for measurement of bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA). The aim was to compare BMD measurements of men and women in this cohort, before and after adjustment for skeletal size. The femoral neck shaft angles (NSA) were also measured manually from the DXA scan printouts. A total of 171 men and 218 women agreed to participate. As expected men had greater bone mineral content and bone area at all sites (p<0.0001) and were taller and heavier (p<0.0001) than women. Men also had significantly higher BMD than women at all regions (p<0.0002), except at the femoral neck or lumbar spine. After correction for skeletal size and body weight, men had statistically significantly lower volumetric BMD at all sites. The measurement of NSA had good intra/interobserver errors and precision (coefficient of variations 0.79%, 1.2% and 1.2%). Men had significantly larger NSAs (mean 130 degrees , range 121-138 degrees ) than women (mean 128 degrees , range 119-137 degrees ). We conclude that there are gender differences in BMD, skeletal size and geometry in middle aged men and women, which together with the subsequent rate of bone loss, may influence fracture risk in later life.

Absorptiometry, Photon↗

PubMed2002

Is distal forearm fracture in men due to osteoporosis?

Although widely regarded as a disease of women, osteoporosis does cause considerable morbidity and mortality in men. The lifetime risk of an osteoporortic fracture for a man is 1 in 12 and 30% of all hip fractures occur in men. In women, low-trauma distal forearm fracture is widely regarded as a typical early manifestation of postmenopausal osteoporosis. Traditionally, this has not been thought to be the case for men. We present a case-control study of 147 men with distal forearm fracture compared with 198 age-matched controls. The controls were selected from a pre-existing database of dual-energy X-ray absorptiometry scans of healthy volunteers. Both groups were sent questionnaires regarding basic demographics, fracture history and risk factors for osteoporosis, and the fracture group was asked to attend for bone densitometry. There were 103 responses from the fracture group (70%), of whom 67 (47%) underwent densitometry. There were 165 (83%) responses from the control group. Secondary causes of osteoporosis could be identified in 51% of the fracture group and 37% of the control group. The fracture group had significantly lower bone mineral density at all sites measured compared with the controls (0.75 g/cm(2) vs 0.85 g/cm(2) at the femoral neck, p<0.0001; 0.95 g/cm(2) vs 1.03 g/cm(2) at the total femur, p = 0.001; and 0.99 g/cm(2) vs 1.06 g/cm(2) at the lumbar spine, p = 0.001). These differences remained after adjusting for age and body mass index ( p<0.0005 at all sites). Overall, 41.8% of the fracture group were osteoporotic in at least one site ( T-score <-2.5 SD below the mean for young men) compared with only 10.3% of controls. This study is the first to demonstrate that men with distal forearm fractures have lower bone mineral density than their peers and a higher risk of osteoporosis.

Absorptiometry, Photon↗

PubMed2002

Osteoporosis.

Osteoporosis is characterised by low bone mass and microarchitectural deterioration of bone tissue, leading to enhanced bone fragility and consequent increase in fracture risk. It is a common condition affecting one in three women and one in 12 men, resulting in substantial morbidity, excess mortality, and health and social services expenditure. It is therefore important to develop strategies to prevent and treat osteoporosis in both men and women. This paper reviews the pathogenesis of primary and secondary osteoporosis, as well as diagnosis, investigation, and management. This should include lifestyle changes to reduce bone loss and decrease the risk of falls, the identification and treatment of secondary causes of bone loss, and specific treatment for osteoporosis. Hormone replacement therapy, raloxifene, bisphosphonates, calcium and vitamin D, calcitonin, and parathyroid hormone have all been shown to improve bone density and decrease the risk of fracture in specific situations. It is important that treatment is tailored to the individual patient, to ensure compliance and optimise the potential benefits.

Accidental Falls↗

PubMed1989

Characterization of the human p53 gene promoter.

Transcriptional deregulation of the p53 gene may play an important part in the genesis of some tumors. We report here an accurate determination of the transcriptional start sites of the human p53 gene and show that the majority of p53 mRNA molecules do not contain a postulated stem-loop structure at their 5' ends. Recombinant plasmids of the human p53 promoter-leader region fused to the bacterial chloramphenicol acetyltransferase gene (cat) were constructed. After transfection into rodent or human cells, a 350-base-pair fragment spanning the promoter region conferred 4% of the CAT activity mediated by the simian virus 40 early promoter/enhancer. We monitored the efficiency with which 15 3' and 5' promoter deletion constructs initiated transcription. Our results show that an 85-base-pair fragment, previously thought to have resided in exon 1, is all that is required for full promoter activity.

Base Sequence↗

PubMed1989

Overexpression of normal human p53 in established fibroblasts leads to their tumorigenic conversion.

Some, but not all, mouse p53 genes are able to cooperate with an activated ras oncogene to transform primary cells. Overexpression of what is presumed to be wild-type murine p53 is sufficient to confer a tumorigenic phenotype on established cell lines. We have investigated the effect of overexpression of normal human p53 genes on the growth and morphology of both primary and established mouse and rat cells. When plasmids containing functional human p53 genes under the control of strong viral promoter/enhancer elements were transfected into NIH3T3 cells or Rat-1 cells, no gross alterations in cell shape or morphology were observed. When stable NIH3T3 transfectants were established by co-transfection of the p53 plasmids with pSV2neo and subsequent selection in medium containing G418, many of the lines generated exhibited altered growth characteristics. While, again, the cells did not form foci above the monolayer and were not capable of growing in soft agar, they showed a reduced dependence on serum for growth, were able to grow to higher saturation densities, and displayed markedly enhanced tumorigenicity when inoculated into nude mice. The expression of human p53 in the transfectants was assessed by immunoblotting with a monoclonal antibody, PAb1801, which is reactive to human but not mouse p53. There was a clear correlation between the extent of p53 overexpression and acquisition of the tumorigenic phenotype. None of nine human p53 constructs was capable of cooperating with an activated ras oncogene to transform primary cells under conditions where a mouse clone, pLTRp53cG, could do so efficiently. None of the human p53 constructs was capable of rescuing primary rat cells from senescence. Taken together, these data show that overproduction of normal human p53 can confer an enhanced tumorigenic phenotype on established fibroblasts and support the idea that mutational activation may be necessary for p53 to express its full oncogenic potential.

Animals↗